title: Steroidal constituents from the starfish Astropecten polyacanthus and their anticancer effects.
abstract: Using various chromatographic methods, four new steroids, astropectenols A-D (1-4), along with three known compounds (5-7) were isolated from a methanol extract of the starfish Astropecten polyacanthus. The structure elucidation was confirmed by spectroscopic methods, including one dimensional (1D)-, 2D-NMR and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The CH2Cl2 fraction and compound 7 exhibit potent cytotoxic effects against HL-60 human leukemia cells with the IC50 of 8.29 µg/mL and 2.70 µM, respectively, comparing to the positive control, mitoxantrone (IC50=6.80 µM). When HL-60 cells were treated with the CH₂Cl₂ fraction or compound 7, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. Investigations for the possible mechanism underlying the induction of apoptosis showed that CH₂Cl₂ fraction or compound 7 induced apoptosis through down-regulation of Bcl-2, up-regulation of Bax, cleavage of caspase-9, cleavage of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) in HL-60 cells. Furthermore, the apoptosis induction of HL-60 cell by CH₂Cl₂ fraction or compound 7 was attended by the decreasing of phospho-extracellular signal-regulated kinase (ERK) 1/2 and C-myc. These results indicated that the CH₂Cl₂ fraction and compound 7 could induce the apoptosis of HL-60 cells via the inactivation of ERK 1/2 and the decrease of C-myc. Our finding suggested the potential using of the CH₂Cl₂ fraction and compound 7 for leukemia treatment.
authors.affiliation: Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST).
authors.forename: Nguyen Phuong
authors.initials: NP
authors.lastname: Thao
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Cuong
authors.forename: Bui Thi Thuy
authors.initials: BT
authors.lastname: Luyen
authors.forename: Nguyen Hoai
authors.initials: NH
authors.lastname: Nam
authors.forename: Pham Van
authors.initials: PV
authors.lastname: Cuong
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Thanh
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Nhiem
authors.forename: Tran Thi Hong
authors.initials: TT
authors.lastname: Hanh
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.forename: Phan Van
authors.initials: PV
authors.lastname: Kiem
authors.forename: Chau Van
authors.initials: CV
authors.lastname: Minh
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008968:Molecular Conformation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013215:Starfish / Q000737:chemistry* / Q000378:metabolism; D013256:Steroids / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D013256:Steroids; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053453:Caspase 9